This project is designed to investigate the mechanisms whereby maternal allergic status during pregnancy and infant immune characteristics, early in life, are associated with the subsequent development of markers of asthma risk in children. The Specific Aims of the project are 1) to investigate mechanisms by which allergic mothers may increase the likelihood of development of an asthma-related allergic predisposition in their children; 2) to characterize the immunologic response following viral lower respiratory tract illnesses (LRIs) in relation to allergic predisposition of the infant; and 3) to determine the relation of the infant's allergic predisposition at birth and immune response with LRIs to the subsequent development of immune system markers of asthma risk. The application hypothesize that a T helper cell (Th2) skew (as indicated by elevated production of IL-4 and IL-5 from stimulated peripheral blood mononuclear cells PBMCs) will be observed at least by age three years in children who: a) have mothers with active allergic rhinitis or Th2 cytokine profiles in pregnancy; b) have Th2 profiles early in life and develop wheezing LRIs; or c) develop early sensitization to the mold Alternaria. The project will enroll four hundred women, half with physician-diagnosed allergic rhinitis, in the third trimester of pregnancy and follow their infants from birth through the first five years of life. The principal outcomes considered will be indicators of immune system function (cytokine profiles from mitogen- stimulated PBMCs, total serum IgE levels, allergen-specific IgE levels, skin test reactivity) in the children at birth, one year, three years and five years. Similar tests of immune system function will be conducted on both the mother and father, and data obtained regarding respiratory symptoms. Blood will be obtained at the time of the first physician-diagnosed LRI, to assess the cytokine response. Serologies to respiratory syncytial virus (RSV) will be obtained at twelve months of age. A comprehensive evaluation of immune system markers for risk of asthma will be conducted at age five. It is the intent of his project to provide knowledge of the immunological roots for the development of asthma in childhood, from which individuals might be identified for whom intervention might be critical; furthermore, it is intended that this information will assist in the development of effective and specific strategies for primary prevention of asthma.